Covalent binding of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-glycolyl-2-aminofluorene to rat hepatocyte DNA: in vitro and cell-suspension studies.

Covalent binding of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-glycolyl-2-aminofluorene to rat hepatocyte DNA: in vitro and cell-suspension studies.
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N-羟基-N-乙酰基-2-氨基芴和 N-羟基-N-乙醇酰基-2-氨基芴与大鼠肝细胞 DNA 的共价结合:体外和细胞悬浮研究。

DOI:
10.1021/tx00001a008
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发表时间:
1988
影响因子:
4.1
通讯作者:
Wiebkin,P
Wiebkin,P
中科院分区:
医学3区
文献类型:
--
作者:
Corbett,MD;Lim,LO;Corbett,BR;Johnston,JJ;Wiebkin,P

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与之前的文献报道一致,N-OH-AAF通过胞浆酶(包括β-酰基转移酶和磺基转移酶)的作用与DNA广泛结合。微粒体酶组分也催化结合DNA,这一过程完全抑制对氧磷。N-OH-GAF与DNA的共价结合仅在S ′-磷酸腺苷-S ′-磷酸硫酸盐存在下才被胞质酶催化到显著程度,这表明磺基转移酶的作用。N-OH-GAF与DNA的共价结合通过胞浆β-酰基转移酶的作用是最小的,这证实了我们早期的观察,N-OH-GAF是这种酶的有效自杀抑制剂。微粒体组分催化N-OH-GAF与DNA结合的速率约为N-OH-AAF所观察到的速率的两倍。在N-OH-AAF结合的情况下,这种微粒体催化的NOH-GAF结合被对氧磷阻止。基于这些结果和对这种结合所涉及的酶机制的了解,提出了相对于由N-OH-AAF生物活化产生的那些加合物,由IV-OH-GAF产生的核酸加合物应具有更高百分比的保留酰基的加合物。
In agreement with the prior literature reports, N-OH-AAF was extensively bound to DNA through the action of cytosol enzymes, including both,-acyltransferase and sulfotransferase. The microsomal enzyme fraction also catalyzed binding to DNA, and this process was completely inhibited by paraoxon. The covalent binding of N-OH-GAF to DNA was catalyzed by cytosol enzymes to a significant extent only in the presence of S'-phosphoadenosine-S'-phosphosulfate, which suggests the action of sulfotransferase. Covalent binding of N-OH-GAF to DNA was minimal through the action of cytosolic,-acyltransferase, which confirms our earlier ob-servation that N-OH-GAF is a potent suicide inhibitor of this enzyme. The microsomal fraction catalyzed the binding of N-OH-GAF to DNA at a rate that was about twice that observed for N-OH-AAF. As in the case of N-OH-AAF binding, this microsomal-catalyzed binding of NOH-GAF was prevented by paraoxon. On the basis of these results and from a knowledge of the enzymatic mechanisms involved in such binding, it was proposed that the nucleic acid adducts from IV-OH-GAF should possess a much higher percent of adducts which retain the acyl group relative tothose adducts resulting from N-OH-AAF bioactivation.
给予 4-氨基联苯的狗的尿液中存在 N-羟基-4-氨基联苯的葡萄糖醛酸结合物的证据。
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影响因子: 5.8
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发表时间: 1982
期刊: ChemInform
影响因子: --
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DOI: --
发表时间: 1977
影响因子: 5.8
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DOI: 10.1021/jm00349a015
发表时间: 1982
影响因子: 7.3
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H. Yeh;P. E. Hanna
通讯作者: P. E. Hanna